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Development of humanized mouse with functional immune systems

Research Project

Project/Area Number 23590561
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

TAKAHASHI Takeshi  公益財団法人実験動物中央研究所, その他部局等, 室長 (80335215)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヒト化マウス / T細胞 / 胸腺 / アレルギー / HLA-DR / IgG
Research Abstract

Humanized mice, in which human hematopoietic and immune systems are reconstituted in severe immunodeficient NOG mice by transplanting human hematopoietic stem cells, have a lot of attention. In the humanized mouse, humoral immune responses against exogenous substances are generally weak. IgG responses, especially, have been difficult to induce. To improve the immune systems, we established a novel mouse strain which expresses human HLA class II genes. We found that the HLA-DR4 expressing NOG mice could produce antigen specific human IgG responses, when they were transplanted with HSC from HLA-haplotype identical donors. This model will be useful to study human immune responses and in developing various therapeutic drugs.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (35 results)

All 2013 2012 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (24 results) Book (1 results)

  • [Journal Article] Establishment of a Human Allergy Model Using Human IL-3/GM-CSF-Transgenic NOG Mice2013

    • Author(s)
      Ito R, Takahashi T, Katano I, Kawai K, Kamisako T, Ogura T, Ida-Tanaka M, Suemizu H, Nunomura S, Ra C, Mori A, Aiso S, Ito M
    • Journal Title

      Journal of Immunology

      Volume: 191 Pages: 2890-2899

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic proliferation of naive CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Kawabe T, Sun SL, Fujita T, Yamaki S, Asao A, Takahashi T, So T, Ishii N
    • Journal Title

      Journal of Immunology

      Volume: 190 Pages: 5788-5798

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Y-Chromosome-linked B- and NK-cell deficiency in mice2013

    • Author(s)
      Sun SL, Horino S, Nakadai A, Kawabe T, Asao A, Takahashi T, So T, Funayama R, Ishii N
    • Journal Title

      Journal of Immunology

      Volume: 190 Pages: 6209-6220

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a Human Allergy Model Using Human IL-3/GM-CSF-Transgenic NOG Mice.2013

    • Author(s)
      Ito, R., T. Takahashi, I. Katano, K. Kawai, T. Kamisako, T. Ogura, M. Ida-Tanaka, H. Suemizu, S. Nunomura, C. Ra, A. Mori, S. Aiso, and M. Ito.
    • Journal Title

      J Immunol

      Volume: 191 Issue: 6 Pages: 2890-2899

    • DOI

      10.4049/jimmunol.1203543

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic proliferation of naive CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Tsuyoshi Fujita, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Journal Title

      Journal of Immunology

      Volume: In press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Y-Chromosome-linked B- and NK-cell deficiency in mice2013

    • Author(s)
      Shu-lan Sun, Satoshi Horino, Ari Nakadai, Takeshi Kawabe, Atsuko Asao, Takeshi Takahashi, Takanori So, Ryo Funayama, and Naoto Ishii
    • Journal Title

      Journal of Immunology

      Volume: In press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice2012

    • Author(s)
      Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, Ishii N
    • Journal Title

      PLoS One

      Volume: 7(6)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Current advances in humanized mouse models2012

    • Author(s)
      Ito R, Takahashi T, Katano I, Ito M
    • Journal Title

      Cell Mol Immunol

      Volume: 9(3) Pages: 208-214

    • Related Report
      2013 Final Research Report
  • [Journal Article] Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse2012

    • Author(s)
      Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K
    • Journal Title

      Int Immunol

      Volume: 24 Pages: 243-252

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γc^<null> mouse2012

    • Author(s)
      Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K.
    • Journal Title

      Int Immunol

      Volume: 24 Issue: 4 Pages: 243-52

    • DOI

      10.1093/intimm/dxs045

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトIL-3/GM-CSFトランスジェニックNOGマウスを用いたヒトアレルギーモデルの開発2013

    • Author(s)
      伊藤亮治、片野いくみ、高橋武司、川井健司、上迫努、布村聡、相磯貞和、伊藤守
    • Organizer
      第60回日本実験動物学会総会
    • Place of Presentation
      つくば/茨城
    • Related Report
      2013 Final Research Report
  • [Presentation] IgE-mediated allergic responses in human mast cells in humanized NOG mice expressing human IL-3 and GM-CSF2013

    • Author(s)
      Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Satoshi Nunomura, Chisei Ra, Akio Mori, Sadakazu Aiso, Mamoru Ito
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milano
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional NK cells developed from human hematopoietic stem cell in human interleukin-2 transgenic NOG mice2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milano
    • Related Report
      2013 Final Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 trasngenic NOG mice2013

    • Author(s)
      TakeshiTakahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milano
    • Related Report
      2013 Final Research Report
  • [Presentation] Human mast cell mediated allergic responses in humanized NOG mouse expressing human IL-3 and GM-CSF2013

    • Author(s)
      Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      Seoul
    • Related Report
      2013 Final Research Report
  • [Presentation] Predominant development of mature and functional human NK Cells in a novel human IL-2 producing transgenic NOD-scid,IL-2Rg KO (NOG) mouse2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      Seoul
    • Related Report
      2013 Final Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 trasngenic NOG mice2013

    • Author(s)
      TakeshiTakahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      Seoul
    • Related Report
      2013 Final Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 transgenic NOG mice2013

    • Author(s)
      高橋武司、片野いくみ、伊藤亮治、伊藤守
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張/千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] Characterization of human Eosinophil in HSC-transferred NOG-human IL-5 transgenic mice2013

    • Author(s)
      片野いくみ、高橋武司、伊藤亮治、伊藤守
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張/千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] Pathology of cutaneous xeno-GVHD in human CD4 T cell transplanted NOG mice2013

    • Author(s)
      伊藤亮治、片野いくみ、高橋武司、伊藤守
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張/千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] IgE-mediated allergic responses in human mast cells in humanized NOG mice expressing human IL-3 and GM-CSF2013

    • Author(s)
      Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Satoshi Nunomura, Chisei Ra, Akio Mori, Sadakazu Aiso, Mamoru Ito
    • Organizer
      15th International congress of Immunology
    • Place of Presentation
      ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional NK cells developed from human hematopoietic stem cell in human interleukin-2 transgenic NOG mice2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      15th International congress of Immunology
    • Place of Presentation
      ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 trasngenic NOG mice2013

    • Author(s)
      TakeshiTakahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito
    • Organizer
      15th International congress of Immunology
    • Place of Presentation
      ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Human mast cell mediated allergic responses in humanized NOG mouse expressing human IL-3 and GM-CSF.2013

    • Author(s)
      Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      ソウル
    • Related Report
      2013 Annual Research Report
  • [Presentation] Predominant development of mature and functional human NK Cells in a novel human IL-2 producing transgenic NOD-scid,IL-2Rg KO (NOG) mouse2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      ソウル
    • Related Report
      2013 Annual Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 trasngenic NOG mice.2013

    • Author(s)
      TakeshiTakahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito
    • Organizer
      4th International workshop on humanized mice
    • Place of Presentation
      ソウル
    • Related Report
      2013 Annual Research Report
  • [Presentation] Characterization of human Eosinophil in HSC-transferred NOG-human IL-5 transgenic mice2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pathology of cutaneous xeno-GVHD in human CD4 T cell transplanted NOG mice.2013

    • Author(s)
      Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Mamoru Ito
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Retrogenic expression of human TCR in HLA-DR4 transgenic NOG mice2013

    • Author(s)
      TakeshiTakahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Characteristics of NK cells developed from human hematopoietic stem cell in human interleukin-2 transgenic NOG mice2012

    • Author(s)
      Katano Ikumi, Ito Ryoji, Takahashi Takeshi, Ito Mamoru
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional maturation of human myeloid cells in a NOD/SCID/IL2rgnull(NOG) transgenic humanized mouse strain expressing human IL-3 and GM-CSF2012

    • Author(s)
      Ito Ryoji, Takahashi Takeshi, Katano Ikumi, Kawai Kenji, Nunomura Satoshi, Ra Chisei, Kamisako Tsutomu, Aiso Sadakazu, Ito Mamoru
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] Homeostatic proliferation occurs iin mesenteric lymph nodes and supplies effector memory CD4 T cells in the intestine2012

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] Induction of human humoral immune repsonses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/gc null mouse

    • Author(s)
      鈴木真紀子、高橋武司、片野いくみ、伊藤亮治、伊藤守、張替秀郎、石井直人、菅村和夫
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      千葉幕張
    • Related Report
      2011 Research-status Report
  • [Presentation] Induction of human humoral immune repsonses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/gc null mouse

    • Author(s)
      高橋武司
    • Organizer
      The 3rd International workshop on humanized mouse
    • Place of Presentation
      ピッツバーグ
    • Related Report
      2011 Research-status Report
  • [Book] Humanized Mice for HIV Research2013

    • Author(s)
      Takeshi Takahashi
    • Publisher
      Springer
    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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